Expression of MDM2 mRNA, MDM2, P53 and P16 Proteins in Urothelial Lesions in the View of the WHO 4th Edition Guidelines as A Molecular Insight towards Personalized Medicine

AIM: Here we imposed a multimarker molecular panel composed of P53, MDM2 protein & mRNA & P16 with the identification of sensitive and specific cut offs among the Egyptian urothelial carcinomas bilharzial or not emphasize the pathological and molecular classifications, pathways and prognosis as a privilege for adjuvant therapy.METHODS: Three hundred and ten urothelial lesions were pathologically evaluated and grouped as follows: 50 chronic cystitis as benign, 240 urothelial carcinomas and 20 normal bladder tissue as a control. Immunohistochemistry for MDM Protein, P16 & p53 and In Situ Hybridization for MDM2mRNA were done.RESULTS: MDM2mRNA overexpression correlated with low grade low stage non invasive tumors, while P53 > 40% & p16 < 10% cut offs correlated with high grade high stage invasive carcinomas & bilharzial tumors (P=0.000).CONCLUSION: MDM2mRNA overexpression vs. P53 > 40% & P16 < 10% constitutes a multimarker molecular panel with significant cut offs, proved to distinguish low grade, low stage non invasive urothelial carcinomas (MDM2mRNA overexpression, P53 < 40%, P16 > 10%) from high grade, high stage invasive urothelial carcinomas (with p53 > 40, p16 < 10% & absent MDM2mRNA overexpression). Combined P53 > 40 & p16 < 10%, together with the histopathological features can distinguish in situ urothelial lesions from dysplastic and atypical lesions

Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007-2014.

INTRODUCTION: Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. METHODS: Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. RESULTS: At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. CONCLUSIONS: Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is important to monitor changes in the etiology, seasonality and severity of pathogens of interest

Expression of FGFR3 Protein and Gene Amplification in Urinary Bladder Lesions in Relation to Schistosomiasis

BACKGROUND: Bladder cancer represents the fifth most common malignancy worldwide and a major cause of cancer-related morbidity and death. Incidence and mortality rates have remained relatively constant over the past four decades. Urothelial bladder cancers have identified multiple risk factors.AIM: We aimed at evaluating the expression of the FGFR3 protein and gene amplification in the urothelial cells of neoplastic and non-neoplastic urothelial lesions of the urinary bladder, and correlation with tumour grade, stage and associated bilharziasis.MATERIAL AND METHODS: One hundred and five different urinary bladder lesions were studied, including 15 cystitis cases (9 bilharzial and 6 non-bilharzial cystitides), 75 urothelial carcinoma cases (18 bilharzial associated and 57 non-bilharzial associated) and 15 squamous cell carcinoma associated with bilharziasis, beside 5 control cases. Data concerning age, sex, tumour grade, stage, and associated bilharziasis were obtained. Each case was studied for FGFR3 expression, and FISH technique was applied on forty malignant cases that show high protein expression.RESULTS: The highest incidence of cystitis was in the fourth decade while of bladder cancer was in the seventh decade. Tumour grade was correlated significantly with tumour stage. FGFR3 correlates significantly with tumour grade, stage and with a bilharzial infestation. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours.CONCLUSIONS: FGFR3 overexpression in malignant cases was significantly higher than in chronic cystitis. FGFR3 gene amplification was reported mainly in low grade and NNMBIC tumours. FGFR3 may be further studied as a subject for target therapy of bladder cancer

Expression of ERG Protein and TMRPSS2-ERG Fusion in Prostatic Carcinoma in Egyptian Patients

AIM: Prostate cancer (PCa) is the second most common cancers in men worldwide. Its incidence can be influenced by several risk factors including genetic susceptibility. Therefore the search for the expression of a certain gene (ERG) and its rearrangement could give us clues for proper identification of PCa. And the study of ERG expression and its comparison to FISH in Egyptian patients can show whether ERG immunophenotype could be used instead of FISH, as it is cheaper.MATERIALS AND METHODS: This study was performed on 85 cases of PCa, showing 30 cases with HGPIN and 30 cases of prostatic hyperplasia. All were immunohistochemistry stained using ERG monoclonal rabbit antihuman antibody was used (clone: EP111). FISH analysis was performed in 38 biopsies of PCa cases to detect TMRPSS2-ERG rearrangement using the FISH ZytoLight TriCheck Probe (SPEC TMRPSS2-ERG).RESULTS: ERG expression was found in 26% of PCa cases and 20% of HGPIN cases. FISH analysis showed fusion of 21 cases of PCa (out of 22 cases showing ERG immunoexpression).CONCLUSION: Our findings emphasise that only malignant and pre-malignant cells and not benign cells from the prostate stain positive. ERG expression may offer a simpler, accurate and less costly alternative for evaluation of ERG fusion status in PCa

Time–cost tradeoff analysis considering funding variability and time uncertainty

This paper presents a linear programming model for solution of the time–cost tradeoff problem. Although several analytical models have been developed for time–cost optimization (TCO), some of them mainly focused on projects where the contract duration is fixed. The optimization objective is therefore restricted to identify the minimum total cost only. Another group have primarily focused on project duration minimization. The model presented here considers scheduling characteristics that were ignored simultaneously in prior research. In the new formulation, variability of funding and uncertainty of project duration are considered simultaneously. A chance-constrained programming is used to incorporate the variability of funding, which is quantified by the coefficient of variation. The financial feasibility expressed as a stochastic constraint, which transformed into a deterministic equivalent at a pre-specified confidence level. Also, the project duration uncertainty incorporated into the model by applying PERT in scheduling and then the uncertainty is quantified by the coefficient of variation at a pre-specified confidence level. A system of objective function, which is minimizing direct cost and the group of constraints are solved by means of Lindo software. Two examples are conducted to demonstrate the model performance and its contributions. Four scenarios were adopted in solving the example problems to reflect the effect of each of funding variability and time uncertainty on project cost and duration. The results revealed that with 95% confidence level: 10% variability in funding versus neglecting it, would increase direct cost with 20% approximately for a pre-specified project deadline. Also, 10% variability in time versus neglecting it, would increase duration in range from 16.5% to 30% approximately, for a pre-specified direct cost. Also, considering 10% variability in funding and time would increase direct cost with more than 25% for a pre-specified project deadline. In parallel, an increase in project duration, more than 30% will occur for a pre-specified direct cost

Insulin resistance in obese pre-pubertal children: Relation to body composition

Background: Abdominal obesity is a strong determinant of obesity related metabolic complications. Data about pre-pubertal children are scarce. The aim of this study is to assess the presence of insulin resistance using different insulin sensitivity indices and investigate its relationship with abdominal fat distribution by Dual energy X-ray absorptiometry scan (DXA). Secondary outcome is to determine the frequency of the metabolic syndrome components. Subjects and methods: Twenty-three pre-pubertal obese children were recruited (14 females, 9 males). Height, weight, body mass index (BMI), waist and hip circumferences, waist to hip ratio, and blood pressure were measured. Fasting blood samples were withdrawn for glucose, insulin, lipid profile, thyroid and liver functions. Patients underwent oral glucose tolerance testing (OGTT) and DXA scan for body composition. Insulin sensitivity was determined using homeostasis model assessment for insulin resistance (HOMA-IR), fasting glucose to insulin ratio, Matsuda, and Cederholm indices. Results: All patients had BMI, waist circumference, and DXA trunk fat more than 2 SDS. Mean fasting glucose, insulin, fasting glucose to insulin ratio, 120 min glucose and HOMA-IR were within normal limits, but mean Matsuda and Cederholm indices exceeded cut off limits. Dyslipidaemia was detected in 13 patients (56.5%), disturbed glucose homeostasis in 8 patients (34.8%), and systolic hypertension in 1 patient (4.3%). Metabolic syndrome diagnosis was established in three patients (13%). More insulin resistant patients were detected by Matsuda index. Trunk fat SDS correlated with Matsuda and Cederholm indices only. Conclusion: Dysglycaemia and dyslipidaemia are common among pre-pubertal obese children. Insulin sensitivity indices based on OGTT are superior to fasting indices in identifying at risk children. OGTT should be included in assessing obese children with BMI > 2 SDS. DXA scanning has limited value for this purpose in clinical settings

Constitutional Delay of Growth and Puberty: the Patient’s Perspective

Introduction: Constitutional delay of growth and puberty (CDGP) is a common cause of psychosocial upset among adolescents and their families. Concerns about reduced final height often urge patients to ask for urgent treatment rather than to wait for observation.Aim: The main objective is to evaluate the concerns, knowledge, understanding, and expectations of a group of children with CDGP and their families. Secondary objective is to study the auxological and socioeconomic characteristics of the patients.Patients and Methods: Forty nine patients with CDGP were included. Fifteen were followed for two years, and seven until final height. Patients and parents completed a designed question sheet to identify their concerns, knowledge, expectations from treatment, and willingness to follow up for observation. Socioeconomic standard scoring and anthropometric evaluation were performed.Results: 59.2% presented because of the concern of the whole family. There was a delay of 1.8 years between the time when patients were concerned about short stature and/or delayed puberty and presentation to clinic The delay was greatest in patients who stopped following up. Twenty seven patients (55.1%) were of low socioeconomic background, 17 (34.7%) were medium low, and 5 (10.2%) were medium high. 69.4% of patients were concerned about their height, not puberty. Two thirds were not convinced that shortness was not due to growth hormone deficiency and that treatment if needed would be sex hormones. 69.4% were not convinced to follow up without treatment.Conclusion: Short stature rather than late puberty is usually the reason for consultation in CDGP. Incomplete understanding of the condition among families and dissatisfaction with the treatment options available remains a problem even after detailed explanation. Extra effort is needed to raise the awareness and avoid the adverse psychosocial sequels in patients with CDGP

A Point Prevalence Survey of Antibiotic Use in 18 Hospitals in Egypt

Inappropriate antibiotic use leads to increased risk of antibiotic resistance and other adverse outcomes. The objectives of the study were to determine the prevalence and characteristics of antibiotic use in Egyptian hospitals to identify opportunities for quality improvement. A point prevalence survey was conducted in 18 hospitals in March 2011. A total of 3408 patients were included and 59% received at least one antibiotic, with the most significant use among persons <12 years and intensive care unit patients (p < 0.05). Third generation cephalosporin were the most commonly prescribed antibiotics (28.7% of prescriptions). Reasons for antibiotic use included treatment of community—(27%) and healthcare-associated infections (11%) and surgical (39%) and medical (23%) prophylaxis. Among surgical prophylaxis recipients, only 28% of evaluable cases received the first dose within two hours before incision and only 25% of cases received surgical prophylaxis for <24 h. The prevalence of antibiotic use in Egyptian hospitals was high with obvious targets for antimicrobial stewardship activities including provision of antibiotic prescription guidelines and optimization of surgical and medical prophylaxis practices

S1 Dataset for "Viral etiology, seasonality and severity of hospitalized patients with severe acute respiratory infections in the Eastern Mediterranean Region, 2007–2014"

Little is known about the role of viral respiratory pathogens in the etiology, seasonality or severity of severe acute respiratory infections (SARI) in the Eastern Mediterranean Region. Sentinel surveillance for SARI was conducted from December 2007 through February 2014 at 20 hospitals in Egypt, Jordan, Oman, Qatar and Yemen. Nasopharyngeal and oropharyngeal swabs were collected from hospitalized patients meeting SARI case definitions and were analyzed for infection with influenza, respiratory syncytial virus (RSV), adenovirus (AdV), human metapneumovirus (hMPV) and human parainfluenza virus types 1-3 (hPIV1-3). We analyzed surveillance data to calculate positivity rates for viral respiratory pathogens, describe the seasonality of those pathogens and determine which pathogens were responsible for more severe outcomes requiring ventilation and/or intensive care and/or resulting in death. At least one viral respiratory pathogen was detected in 8,753/28,508 (30.7%) samples tested for at least one pathogen and 3,497/9,315 (37.5%) of samples tested for all pathogens-influenza in 3,345/28,438 (11.8%), RSV in 3,942/24,503 (16.1%), AdV in 923/9,402 (9.8%), hMPV in 617/9,384 (6.6%), hPIV1 in 159/9,402 (1.7%), hPIV2 in 85/9,402 (0.9%) and hPIV3 in 365/9,402 (3.9%). Multiple pathogens were identified in 501/9,316 (5.4%) participants tested for all pathogens. Monthly variation, indicating seasonal differences in levels of infection, was observed for all pathogens. Participants with hMPV infections and participants less than five years of age were significantly less likely than participants not infected with hMPV and those older than five years of age, respectively, to experience a severe outcome, while participants with a pre-existing chronic disease were at increased risk of a severe outcome, compared to those with no reported pre-existing chronic disease. Viral respiratory pathogens are common among SARI patients in the Eastern Mediterranean Region. Ongoing surveillance is important to monitor changes in the etiology, seasonality and severity of pathogens of interest